5-(p-aminobenzene sulfonamido)-1, 3 dimethyl-2, 4 dioxo-6-amino-tetrahydropyrimidineand its preparation



Patented May 23, 1950 p- AMINOBENZENE SULFONAMIDO) 1,3

DIMETHYL-2,4 DIOXO 6 AMINO-[PETRA- HYDROPYRIMIDINE AND ITS PREPARA- TION Andr Demolis, Zoflngen, Switzerland, assignor to Aktiengesellschaft vorm. B. Siegfried, Zofingen,

Switzerland No Drawing. Application June 19, 1947, Serial No. 755,721.- In Switzerland March 12, 1942 Section 1, Public Law 690, August 8, 1948 Patent expires March 12, 1962 6 Claims.

1 This invention relates to new paraaminobenzene sulfonamides and processes for makin the same and more particularly to B-(p-aminobenzene sulfonamido)-l,3-dimethyl-2,4-dioxo-6- amino-tetrahydropyrimidine and its production.

In accordance with one embodiment a compound containing the radical of an acylated sulfanilic acid, for example, a derivative of an acyl sulfanilic acid such as a halide, an ester, or the free acid itself, is condensed with 1,3-dimethyl-2,4- dioxo-5,6-diamino tetrahydropyrimidine, (such as disclosed in Beilstein volume 25, page 482, and Beilstein supplemental volume 25, page 696), and the product of this reaction, having a melting point of 268-2'72 C., is treated with a, hydrolyzing agent. The 5-(p-aminobenzene sulfonamido)- 1,3 dimethyl 2,4 dioxo-fi-amino tetrahydropyrimidine is a white crystalline powder having a melting point of 250-252 C. and is soluble in alkalies and acids. It is used as a pharmaceutical product or for the preparation of such products.

Other known reactive benzene sulfonic acid compounds, such as the acids themselves or their derivatives having a benzene sulfonic acid radical and having a nitrogen-containing substituent convertible into an amino group in the para position, may be used in this process. The reactive benzene sulfonic acid compounds of this invention may be represented by the formula:

ene sulfonic acid compounds such as the acids themselves, their halides, or their esters. More is then filtered.v and washed. The so-obtained melting point of 268272 C. It is hydrolyzed in a dilute alcoholic hydrochloric acid solution, then an excess of sodium acetate is added, and the obtained B-(p-aminobenzene sulfonamido) -1,3- dimethyl 2,4-dioxo-6-amino-tetrahydropyrimidine is filtered and dried. It is a white crystalline powder, which, when pure, melts between 250-252 C. and upon analysis corresponds to the formula C12H1504N5S.

N: calculated: 21.53 per cent, ascertained: 21.50 per cent.

The product is soluble in alkalies and acids and shows the diazo-reaction.

The new compound is efiective against bacteria of the typhus-(Eberthella. typhosa) paratyphus and enteritis-group, oi the dysenteria group and bacterium coli.

It is distinguished by its high insolubility and is resorbed only little by the intestinal mucuous membrane, however suiliciently to suppress the bacillaemia encountered with typhus abdominalis and paratyphus Schottmueller and it produces a local eiiect in the intestinal tract due to its high concentration therein.

Example 2 A suspension of 170 grams 1,3-dimethy1-2,4- dioxo-5,6-diamino-tetrahydropyrimidine in 500 cubic centimeters pyridine is gradually mixed with 230 grams p-nitrobenzene-sulfochloride at room temperature. After the reactants are added, the mixture is heated to 60 C. and stirred at this temperature for one hour. After cooling, 3 liters of water is added andthe mixture allowed to stand for some time, whereupon the mixture is specifically, in such compounds, for example," X

may represent an AcNH-radical where Ac is an acyl radical e. g. the iormyl or acetyl radical or the NOz-radical. The AcNH-radical is converted to the NHz-radical by hydrolysis, while the nitro group is converted to the NHa-radical by conventional procedures using a reducing agent.

Example 1 Sixty-five parts acetyl sulianilic acid chloride is reacted with 44.2 parts of 1,3-dimethyl-2,4- dioxo-5,6-diamino-tetrahydropyrimidine by heating them in a solvent, as, for example, pyridine, on a water bath. The product of this reaction, which is precipitated upon dilution with water,

, mixed with a dilute sodium hydroxide solutionv filtered. The residue is heated several hours with 200 grams of pulverized iron in a dilute solution of ethyl alcohol and hydrochloric acid. Then the ethanol is distilled off and the residue and filtered. After neutralization with hydro- .chloric acid, the 5-(p-amin0benzene-sulf0namido) -1,3-dimethyl 2,4 dioxo-G-amino-tetrahydropyrimidine crystallizes in fine slightly brownish crystals. The desired reaction product is purified by dissolving it in a. dilute sodium hydroxide solution and precipitating it therefrom with hydrochloric acid. The melting point of the purified crystals is 250-252 C.

It will be understood that the examples disclosed herein, the proportions used, and the specific reaction conditions specified are illustrative and thattheinvention is not limited thereto but extends to equilifalentsjencomiiasscd 'with inithe scope of -the"invention which is defined by the appended claims.

I claim:

( 1. A process for producing 5- r(p; -arninobenz ene sulfonamido) 1,3-dimethyle2;'-dioxo-fiaminm. tetrahydropyrimidine which comprises reacting...

a benzene sulfonic acid compound selected from the group consisting of benzene s uli oni c hal ides and benzene sulfonic esters containing substituent convrtible'into'tli' afiiiiio group in the para position selected frorn the group consisting of N02 and aefylamino radicals sulfonaniidoy-lfi-d-imethy1 2j4dioxo 6 amino- V tetrahydropyrimidin'e; which comprises reacting ai-p=acylaminobenzene 'sulfonic acid halide with L3 -dimethyl=2,4-dioxo 5;6 dianiinotetrahydropyrimidine toproduce a fi -(p a'cylamino-ben'zene sulfo'namido') l,3-diinethyl 2,4-dioxo eam'indtetrahydropyrimidin'e, and converting the acyl amino substituentof the obtained 1 reaction prodsulfonamido)-1,3 dirnethyl-ZA-dioifo=6 ainino#' tetrahydropyrimidine which com rises reacting a p-acetylarninobenzene sulforli'c acid chloride With- '1 ;3 f dimethy1=2g4=dioXo-5;6 -diaminotetrahydropyrimidine toproduce a 5- (p=acety1aniinobenzene 'sulfonamidoi -1,3difnethyl=2',4=mono-6-' arnino-tetrahydropyri nidine, ana'converun -sam acetyla'mino substitu'ent of' the obtained-reaction alcoholic hydrochloric 1 acid;

product into Ashe N'Hz groi-ip' by hydrolysis with tetraliyd'rop riinidine which'=cofi1pris'es reacting a pnitrobenzene sulfonic acid halide with 1,3-di- "methyl-2,4-dioxo-5,6 diamino-tetrahydropyrimidine' -t :g produce 5;( p=n itrobenzene suifonamido) ..rimidine=,irandy-converting said nitro substituent of the obtained-rieaction product into the NH:-

5f-fdimethyl-2A-dioxo-6-aminodinewhich comprises reacting a 'fsiil-f onic acid chloride with 1,3-

with 1,3 dimeth 1-2,4-dioxo-Et6:d1amino=tetra-"" "di fi t iy fii di i d a no t ahydropyhydropyrimidine to produce a 5-(benzenesulfpn.-

amido) 1,3-dimethy1-2,4-dioxo-6-amin0-tetrarirnidine produce 5- ('p-nitrobenzene sulfonf 1-,'3 methyl-2,4-dioxo 6 amino-tetrahydropyrimidine, and converting said nitro substitiint of the obtained reaction product into the NHz-group with a reducing agent.

The following"references eclectic m we Nurhbe r flange bar 2135 333 .Qysinec "L -June 13;,1344;

2,407,966: 'Sprague Sept 1-7-,=1946 A to pry fla Switzerland c July '16, 19413"- OTHER. 5 REFERENCES 

1. A PROCESS FOR PRODUCING 5-(P-AMINOBENZENE SULFONAMIDO) - 1,3-DIMETHYL-2,4-DIOXO-6-AMINOTETRAHYDROPYRIMIDINE WHICH COMPRISES REACTING A BENZENE SULFONIC ACID COMPOUND SELECTED FROM THE GROUP CONSISTING OF BENZENE SULFONIC HALIDES AND BENZENE SULFONIC ESTERS HAVING A NITROGENCONTAINING SUBSTITUENT CONVERTIBLE INTO THE AMINO GROUP IN THE PARA POSITION SELECTED FROM THE GROUP CONSISTING OF NO2 AND ACYLAMINO RADICALS WITH 1,3 - DIMETHYL-2,4-DIOXO-5,6-DIAMINO-TETRAHYDROPYRIMIDINE TO PRODUCE A 5-(BENZENE-SULFONAMIDO) - 1.3-DIMETHYL-2,4-DIOXO-6-AMINO-TETRAHYDROPYRIMIDINE HAVING SAID NITROGEN-CONTAINING SUBSTITUENT IN THE PARA POSITION OF THE BENZENE RING, AND CONVERTING SAID NITROGEN-CONTAINING SUBSTITUENT OF THE OBTAINED REACTION PRODUCT INTO THE NH2-GROUP.
 6. A NEW COMPOUND, 5-9P-AMINOBENZENE SULFONAMIDO)-1,3-DIMETHYL-2,4-DIOXO-6-AMINO -TETRAHYDROPYRIMIDINE. 